February 2024: Antibiotic antibodies, antibiotic conjugates, and antimicrobials!

In the realm of combating bacterial infections and antimicrobial resistance, antibodies are beginning to stand out as a therapy with innovative strategies and engineering methods continually being published. This month’s trend will focus on the developments in ‘antibiotic antibodies’, antibody-antibiotic conjugates, and antibody antimicrobials, which are particularly important for immunocompromised patients.

This February, Yang et al. published a paper reporting the discovery of a monoclonal antibody (mAb) named Pse-MAB1 that targets cell-surface Pseudaminic acid (Pse) of Acinetobacter baumannii strains with a direct bactericidal effect. This strong killing effect was exhibited even in the absence of the host complements or other immune factors, which has never before been shown by antibodies alone, as the therapeutic effects typically involve neutralization of pathogens, activation of the host complement system, or facilitation of phagocytosis of pathogens.

Pse-MAB1 works by mediating bacterial aggregation and triggering metabolic disorders and oxidative injury, which causes bacterial cell death. However, the metabolic dysregulation as a direct downstream function of Pse-MAB1 remains to be studied, as the proteins are not yet characterized yet.

Meanwhile, a different research team has been focusing on a different approach to target bacterial infections. Qin et al. proposed a mechanism for an antibody-antibiotic conjugate (AAC) targeted therapy for orthopedic implant-associated intracellular S. aureus infections. The AAC consists of a human mAb (M0662) conjugated with vancomycin, thus targeting the surface antigen of S. aureus and mediating endocytosis to kill bacteria after entry into the cell.

Unfortunately, as time progresses, more bacterial pathogens are becoming resistant to developed antibiotics, resulting in ineffective medicines and persistent infections. Microbes which are resistant to multiple antimicrobials are named multidrug resistant (MDR), also known as superbugs, and while it is a natural process, this is usually due to improper drug usage and infection management. For instance, 0.05-0.2% of patients in a hospital will contract pneumonia, typically from the superbug Pseudomonas aeruginosa.

A study by Simonis et al. published in Cell revealed the discovery of highly neutralizing human antibodies targeting P. aeruginosa (PA), which is currently drug resistant. Chronic PA infection leads to the development of anti-PcrV antibodies, and highly vulnerable C-terminal PcrV epitopes are targeted by neutralizing antibodies. Their results demonstrated how these anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. This means that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA.